In process & finished products quality control test of capsule, prepared by Arpit suralkar

1. In process & finished products
quality control test for
pharmaceuticals (Capsules)
Prepared by
Arpit rajaram suralkar
M pharmacy in quality Assuarance
First year.

2. IPQC AND FPQC TESTS FOR PHARMACEUTICAL
CAPSULES
• Physical parameters of pharmaceutical capsules that are controlled by
IPQC tests are temperature, pressure, relative humidity, particle size, color,
fill weight, shell weight, softgel ribbon thickness, softgel seal thickness,
softgel shell moisture level, softgel hardness, disintegration time etc. FPQC
test for pharmaceutical capsules are assay, fill weight, uniformity of
content, uniformity of mass, mass variation, microbiological test,
disintegration test, dissolution test, stability test etc. IPQC and FPQC test
for pharmaceutical capsules according to pharmacopoeias are listed below

3. • Appearance
Capsules produced on a small or a large scale should be uniform in appearance.
Visual or electronic inspection should be undertaken to detect any flaws in the
integrity and appearance of the capsule. Evidence of physical instability is
demonstrated by gross changes in appearance, including hardening or softening,
cracking, swelling, mottling, printing mistake or discoloration of the shell.
Defective capsules should be rejected.
• Size and Shape
Hard capsules are made in a range of sizes, the standard industrial ones in
use today for human medicines range from size from 000 (the largest, 1.40 ml)
to 5 (the smallest, 0.13 ml) are commercially available. Soft gel capsules are
available in variety of shapes such as spherical (0.05–5 ml), ovoid (0.05–7 ml),
cylindrical (0.15– 25 ml), tubes (0.5–0 ml), pear (0.3–5 ml) etc .

4. • Unique Identification Markings
Capsule surfaces may bear symbols or other unique
identification markings for better identification
• Assay
In a capsule an active ingredient is present which is called API.
So to prepare the capsule assay has to be done by using
suitable analytical method to produce good finished product.

5. • Content of Active Ingredients
• For this test a sample of the contents is assayed as
described in individual monographs and calculates the
amount of active ingredient in each capsule. According
to IP the range for the content of active ingredient
stated in the monograph is based on the requirement
that 20 capsules, or such other number as may be
indicated in the monograph, are used in the assay. In
the circumstances where 20 capsules cannot be
obtained, a smaller number, which must not be less
than 5.
• The requirements of the Table 1 apply when the stated
limits are between 90 and 110 percent. For limits other
than 90 to 110 percent, proportionately smaller or
larger allowances should be made.

6. • Content Uniformity Test
• For this test according to BP determine the content of the active ingredient in each of 10
capsules (hard or soft) taken at random using the method given in the monograph or by any
other suitable analytical method of equivalent accuracy and precision. Calculate the
acceptance value (AV) using the following formula:
• │M – X │ + KS
• Where,
• M = Reference value.
• X = Mean of individual content (x1, x2,..., xn) expressed as percentage of the label claim.
• K = Acceptability constant.
• S = Sample standard deviation.
• As per BP capsules comply with the test if not more than one of the individual values thus
obtained is outside the limits 85 to 115 percent of the average value and none is outside the
limits 75 to 125 percent. The capsules fails to comply with the test if more than 3 individual
contents are outside the limits of 85 percent to 115 percent of the average content or if one
or more individual contents are outside the limits of 75 percent to 125 per cent of the
average content. If 2 or 3 individual values are outside the limits 85 to 115 percent of the
average values, repeat the determination using another 20 capsules. The capsules comply
with the test if in the total sample of 30 capsules not more than 3 individual values are
outside the limits 85 to 115 percent and none is outside the limits 75 to 125 percent of the
average value. As stated by IP, BP, USP and PhEur limits for content uniformity (CU) and mass
variation (MV) tests of capsules. According to IP this test is not applicable for capsules
containing multivitamins and trace elements

7. • Uniformity of Mass
• For this test weigh an intact capsule. Open the capsule without losing any
part of the shell and remove the contents as completely as possible. To
remove the contents of a soft capsule the shell may be washed with ether
or other suitable solvent and the shell allowed to stand until the odor of
the solvent is no longer perceptible. Weigh the shell. The weight of the
contents is the difference between the weighing. Repeat the procedure
with a further 19 capsules. Determine the average mass. According to IP,
BP, PhEur and PhInt capsules not more than 2 of the individual masses
deviate from the average mass by more than the percentage deviation
shown in the Table 3 and Table 4 respectively and none deviates by more
than twice that percentage

8. • Mass Variation Test
• For hard capsules according to BP accurately weigh 10 capsules individually, taking care to preserve
the identity of each capsule. Remove the contents of each capsule by suitable means. Accurately
weigh the emptied shells individually, and calculate for each capsule the net mass of its contents by
subtracting the mass of the shell from the respective gross mass. Calculate the active substance
content in each capsule from the mass of product removed from the individual capsules and the
result of the assay. Calculate the AV using the following formula:
• Xi = Wi × A/W
• Where,
• x1, x2,..., xn = Individual estimated contents of the dosage units tested.
• w1, w2,..., wn = Individual masses of the dosage units tested.
• A = Content of active substance (percentage of label claim) obtained using an appropriate analytical
method (assay).
• W = Mean of individual weights (w1, w2,..., wn)
• For soft capsules consistent with BP accurately weigh 10 intact capsules individually to obtain their
gross masses, taking care to preserve the identity of each capsule. Then cut open the capsules by
means of a suitable clean, dry cutting instrument such as scissors or a sharp open blade, and
remove the contents by washing with a suitable solvent. Allow the occluded solvent to evaporate
from the shells at room temperature over a period of about 30 min, taking precautions to avoid
uptake or loss of moisture. Weigh the individual shells, and calculate the net contents. Calculate the
active substance content in each capsule from the mass of product removed from the individual
capsules and the result of the assay. Calculate the AV using the following formula given above.
• According to BP and USP, the requirement is met if the acceptance value of 10 capsules is less than
or equal to 15 percent. If acceptance value is greater than 15 percent, test the next 20 capsule and
calculate the acceptance value. The requirements are met if the final acceptance value of the 30
capsule is less than or equal to 15 percent and no individual content of the capsule is less than (1 –
25 × 0.01) M or more than (1 + 25 × 0.01)M in calculation of acceptance value under mass variation
or content uniformity.

9. • Disintegration Test
• The USP disintegration apparatus consist of 6 glass tubes that are 3 inches long, open at the
top, and held against a 10-mesh screen at the bottom end of the basket rack assembly. To
test for disintegration time, one capsule is placed in each tube and the basket rack is
positioned in specified medium at 37±2ºC such that capsule remains 2.5 cm below the
surface of the liquid on their upward movement and descend not closer than 2.5 cm from the
bottom of the beaker. A standard motor driven device is used to move the basket assembly
containing the capsules up and down through distance of 5 to 6 cm at a frequency of 28 to 32
cycles per minute. Perforated plastic discs may also be used in the test. These are placed on
the top of capsules and impart an abrasive action to the capsules. The discs may or may not
be meaningful or impart more sensitivity to the test, but they are useful for capsules that
float. Operate the apparatus for the specified time. The capsule complies with the test, if the
capsules

10. • Dissolution Test
• The BP or USP dissolution apparatus (Basket apparatus) consist of a
cylindrical vessel with a hemispherical bottom, which may be covered,
made of glass or other inert, transparent material; a motor; a metallic
drive shaft; and a cylindrical basket. The vessel is partially immersed in a
suitable water bath of any convenient size or heated by a suitable device
such as a heating jacket. The water bath or heating device permits holding
the temperature inside the vessel at 37±0.5°C during the test and keeping
the bath fluid in constant, smooth motion. For this test as per BP and
PhEur place the stated volume of the dissolution medium (±1%) in the
vessel of the specified apparatus. Assemble the apparatus, equilibrate the
dissolution medium to 37±0.5°C. Place 1 capsules in the apparatus, taking
care to exclude air bubbles from the surface of the capsules. Operate the
apparatus at the specified rate. Within the time interval specified, or at
each of the times stated, withdraw a specimen from a zone midway
between the surface of the dissolution medium and the top of the
rotating basket or blade, not less than 1 cm from the vessel wall. Where
multiple sampling times are specified, replace the aliquots withdrawn for
analysis with equal volumes of fresh dissolution medium at 37°C or, where
it can be shown that replacement of the medium is not necessary, correct
for the volume change in the calculation. Keep the vessel covered for the
duration of the test and verify the temperature of the medium at suitable
times

11. Perform the analysis using a suitable assay method as directed in the individual
monograph. Repeat the test with additional capsules. According to BP, USP, PhEur,
PhInt and JP unless otherwise specified in the individual monograph, the requirements
are met if the quantities of active ingredient dissolved from the capsules tested
conform to the following acceptance criteria. Continue testing through the 3 stages
unless the results conform at either S1 or S2. The quantity Q, is the specified amount
of dissolved active substance, expressed as a percentage of the labeled content; the 5
percent, 15 percent, and 25 percent values in the capsule are percentages of the
labeled content so that these values and Q are in the same terms.

12. • Moisture Permeation Test
The USP requires determination of the moisture permeation
characteristics of single-unit and unitdose containers to ensure their
suitability for packaging capsules. The degree and rate of moisture
penetration are determined by packaging the dosage unit together with a
colorrevealing desiccant pellet, exposing the packaged unit to known
relative humidity over a specified time, observing the desiccant pellet for
color change. Any change in color indicates absorption of moisture. By
measuring pretest weight and protest weight of pellet, amount can be
calculated .

13. • Stability Test
The capsule manufacturers routinely conduct accelerated physical
stability tests on all new capsule products as an integral part of the
product development program. The following tests have proved
adequate for determining the effect of the capsule shell content on
the gelatin shell. The tests are strictly relevant to the integrity of the
gelatin shell and should not be confused as stability tests for the
active ingredients in the capsule content. The results of such tests
are used as a guide for the reformulation of the capsule content or
the capsule shell, or for the selection of the proper retail package.
The test conditions for such accelerated stability tests are shown in
above, Table 8. The capsules at these stations are observed
periodically for 2 weeks. Both gross and subtle effects of the
storage conditions on the capsule shell are noted and recorded. The
control capsule should not be affected except at the 80 percent RH
(relative humidity) station, where the capsule would react as
described under the effects of high humidity.

14. • CONCLUSION
• To ensure the quality of pharmaceuticals regulatory
bodies are continually developing their requirements
toward pharmaceutical companies. In pharmaceutical
industry the maximum quality of pharmaceuticals,
depends on the tests performed during manufacturing
and after manufacturing of the pharmaceuticals as per
specifications of the respective pharmacopoeias and
the regulatory requirements of the particular
countries. From the present study it is clearly revealed
though various pharmacopoeias suggest different
types of IPQC and FPQC tests for pharmaceutical
capsules with different specifications and standards but
the main function of the all pharmacopoeias is to
assure the maximum quality of pharmaceuticals for
human health